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1.
Biomol NMR Assign ; 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38822991

ABSTRACT

The odorant binding protein, OBP44a is one of the most abundant proteins expressed in the brain of the developing fruit fly Drosophila melanogaster. Its cellular function has not yet been determined. The OBP family of proteins is well established to recognize hydrophobic molecules. In this study, NMR is employed to structurally characterize OBP44a. NMR chemical shift perturbation measurements confirm that OBP44a binds to fatty acids. Complete assignments of the backbone chemical shifts and secondary chemical shift analysis demonstrate that the apo state of OBP44a is comprised of six α-helices. Upon binding 8(Z)-eicosenoic acid (8(Z)-C20:1), the OBP44a C-terminal region undergoes a conformational change, from unstructured to α-helical. In addition to C-terminal restructuring upon ligand binding, some hydrophobic residues show dramatic chemical shift changes. Surprisingly, several charged residues are also strongly affected by lipid binding. Some of these residues could represent key structural features that OBP44a relies on to perform its cellular function. The NMR chemical shift assignment is the first step towards characterizing the structure of OBP44a and how specific residues might play a role in lipid binding and release. This information will be important in deciphering the biological function of OBP44a during fly brain development.

2.
Carbohydr Polym ; 339: 122235, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38823906

ABSTRACT

This study explored the physicochemical properties and structural characteristics of Agrocybe cylindracea polysaccharides at four developmental stages, as well as their dynamic evolution during maturation. Results showed that the polysaccharides from A. cylindracea water extract exhibited similar structural characteristics across all four maturity stages, despite a significant reduction in yields. Four water-soluble heteroglycans, including one high molecular weight (ACPM-Et50-I) and three low molecular weight (ACPM-Et50-II, ACPM-Et60, ACPM-Et80), were isolated from A. cylindracea at each maturity stage. ACPM-Et50-I was identified as branched heterogalactans, while ACPM-Et60 and ACPM-Et80 were branched heteroglucans. However, ACPM-Et50-II was characterized as a branched glucuronofucogalactoglucan at the tide-turning stage but a glucuronofucoglucogalactan at the pileus expansion stage due to the increase of its α-(1 â†’ 6)-D-Galp. In general, although the structural skeletons of most A. cylindracea heteroglycans were similar during maturation as shown by their highly consistent glycosyl linkages, there were still differences in the distribution of some heteroglucans. This work has for the first time reported a glucuronofucogalactoglucan in A. cylindracea and its dynamic evolution during maturation, which may facilitate the potential application of A. cylindracea in food and biomedicine industries.


Subject(s)
Agrocybe , Water , Water/chemistry , Agrocybe/chemistry , Glucans/chemistry , Polysaccharides/chemistry , Molecular Weight
3.
Liver Int ; 2024 May 08.
Article in English | MEDLINE | ID: mdl-38717072

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent chronic liver disease globally. Non-alcoholic steatohepatitis (NASH) represents an extremely progressive form of NAFLD, which, without timely intervention, may progress to cirrhosis or hepatocellular carcinoma. Presently, a definitive comprehension of the pathogenesis of NAFLD/NASH eludes us, and pharmacological interventions targeting NASH specifically remain constrained. The aetiology of NAFLD encompasses a myriad of external factors including environmental influences, dietary habits and gender disparities. More significantly, inter-organ and cellular interactions within the human body play a role in the development or regression of the disease. In this review, we categorize the influences affecting NAFLD both intra- and extrahepatically, elaborating meticulously on the mechanisms governing the onset and progression of NAFLD/NASH. This exploration delves into progress in aetiology and promising therapeutic targets. As a metabolic disorder, the development of NAFLD involves complexities related to nutrient metabolism, liver-gut axis interactions and insulin resistance, among other regulatory functions of extraneous organs. It further encompasses intra-hepatic interactions among hepatic cells, Kupffer cells (KCs) and hepatic stellate cells (HSCs). A comprehensive understanding of the pathogenesis of NAFLD/NASH from a macroscopic standpoint is instrumental in the formulation of future therapies for NASH.

4.
Biochem Biophys Rep ; 38: 101719, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38708422

ABSTRACT

Empirical studies have indicated that excessive tea consumption may potentially decrease folate levels within the human body. The main active component in green tea, epigallocatechin gallate (EGCG), significantly reduces the concentration of 5-methyltetrahydrofolate (5-MTHF) in both solution and serum. However, our findings also demonstrate that the pro-degradation effect of EGCG on 5-MTHF can be reversed by L-ascorbic acid (AA). Subsequent investigations suggest that EGCG could potentially expedite the degradation of 5-MTHF by generating hydrogen peroxide. In summary, excessive tea intake may lead to reduced folate levels in the bloodstream, yet timely supplementation of AA could potentially safeguard folate from degradation.

5.
Front Oncol ; 14: 1374278, 2024.
Article in English | MEDLINE | ID: mdl-38756651

ABSTRACT

Objective: In physical health examinations, breast sonography is a commonly used imaging method, but it can lead to repeated exams and unnecessary biopsy due to discrepancies among radiologists and health centers. This study explores the role of off-the-shelf artificial intelligence (AI) software in assisting radiologists to classify incidentally found breast masses in two health centers. Methods: Female patients undergoing breast ultrasound examinations with incidentally discovered breast masses were categorized according to the 5th edition of the Breast Imaging Reporting and Data System (BI-RADS), with categories 3 to 5 included in this study. The examinations were conducted at two municipal health centers from May 2021 to May 2023.The final pathological results from surgical resection or biopsy served as the gold standard for comparison. Ultrasonographic images were obtained in longitudinal and transverse sections, and two junior radiologists and one senior radiologist independently assessed the images without knowing the pathological findings. The BI-RADS classification was adjusted following AI assistance, and diagnostic performance was compared using receiver operating characteristic curves. Results: A total of 196 patients with 202 breast masses were included in the study, with pathological results confirming 107 benign and 95 malignant masses. The receiver operating characteristic curve showed that experienced breast radiologists had higher diagnostic performance in BI-RADS classification than junior radiologists, similar to AI classification (AUC = 0.936, 0.806, 0.896, and 0.950, p < 0.05). The AI software improved the accuracy, sensitivity, and negative predictive value of the adjusted BI-RADS classification for the junior radiologists' group (p< 0.05), while no difference was observed in the senior radiologist group. Furthermore, AI increased the negative predictive value for BI-RADS 4a masses and the positive predictive value for 4b masses among radiologists (p < 0.05). AI enhances the sensitivity of invasive breast cancer detection more effectively than ductal carcinoma in situ and rare subtypes of breast cancer. Conclusions: The AI software enhances diagnostic efficiency for breast masses, reducing the performance gap between junior and senior radiologists, particularly for BI-RADS 4a and 4b masses. This improvement reduces unnecessary repeat examinations and biopsies, optimizing medical resource utilization and enhancing overall diagnostic effectiveness.

6.
Mater Today Bio ; 26: 101083, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38757058

ABSTRACT

Directional cell migration is a crucial step in wound healing, influenced by electrical and topographic stimulations. However, the underlying mechanism and the combined effects of these two factors on cell migration remain unclear. This study explores cell migration under various combinations of guided straight line (SL) spacing, conductivity, and the relative direction of electric field (EF) and SL. Electrowriting is employed to fabricate conductive (multiwalled carbon nanotube/polycaprolactone (PCL)) and nonconductive (PCL) SL, with narrow (50 µm) and wide (400 µm) spacing that controls the topographic stimulation strength. Results show that various combinations of electrical and topographic stimulation yield significantly distinct effects on cell migration direction and speed; cells migrate fastest with the most directivity in the case of conductive, narrow-spacing SL parallel to EF. A physical model based on intercellular interactions is developed to capture the underlying mechanism of cell migration under SL and EF stimulations, in agreement with experimental observations. In vivo skin wound healing assay further confirmed that the combination of EF (1 V cm-1) and parallelly aligned conductive fibers accelerated the wound healing process. This study presents a promising approach to direct cell migration and enhance wound healing by optimizing synergistic electrical and topographic stimulations.

7.
Cognition ; 249: 105808, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38776622

ABSTRACT

This study aimed to determine the unit for switching representational states in visual working memory (VWM). Two opposing hypotheses were investigated: (a) the unit of switching being a feature (feature-based hypothesis), and (b) the unit of switching being an object (object-based hypothesis). Participants (N = 180) were instructed to hold two features from either one or two objects in their VWM. The memory-driven attentional capture effect, suggesting that actively held information in VWM can cause attention to be drawn towards matched distractors, was employed to assess representational states of the first and second probed colors (indicated by a retro-cue). The results showed that only the feature indicated to be probed first could elicit memory related capture for the condition of separate objects. Importantly, features from an integrated object could guide attention regardless of the probe order. These findings were observed across three experiments involving features of different dimensions, same dimensions, or perceptual objects defined by Gestalt principles. They provide convergent evidence supporting the object-based hypothesis by indicating that features within a single object cannot exist in different states.

8.
J Agric Food Chem ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38778434

ABSTRACT

Polysaccharides derived from Agrocybe cylindracea have been demonstrated to exhibit various bioactivities. However, studies on their structural characteristics during the growth process are limited. This study aimed to compare the physicochemical properties and structural characteristics of alkali-extracted polysaccharides from A. cylindracea fruiting bodies (JACP) across four growth stages. Results showed that the extraction yields and protein levels of JACP declined along with the growth of A. cylindracea, while the contents of neutral sugar and glucose increased significantly. However, JACP exhibited structural characteristics similar to those across the four stages. Four polysaccharide subfractions were isolated from each growth stage, including JACP-Et30, JACP-Et50, JACP-Et60, and JACP-Et70. JACP-Et30 from the four stages and JACP-Et50 from the initial three stages were identified as heteroglucans with ß-1,3-d-Glcp and ß-1,6-d-Glcp residues as main chains, respectively. However, other subfractions were considered as ß-1,6-d-glucans containing minor glucuronic acid. These subfractions were predominantly replaced by Glcp residues at the O-3 and O-6 positions. Overall, while JACP exhibited variable physicochemical properties, its structural characteristics remained stable during the growth process, offering new insights into its potential applications in the food and medicinal industries.

9.
Sci Adv ; 10(21): eadn9017, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38787955

ABSTRACT

Dynamic control of circular dichroism in photonic structures is critically important for compact spectrometers, stereoscopic displays, and information processing exploiting multiple degrees of freedom. Metasurfaces can help miniaturize chiral devices but only produce static and limited chiral responses. While external stimuli can tune resonances, their modulations are often weak, and reversing continuously the sign of circular dichroism is extremely challenging. Here, we demonstrate the dynamically tunable chiral response of resonant metasurfaces supporting chiral bound states in the continuum combining them with phase-change materials. Phase transition between amorphous and crystalline phases allows for control of chiral response and varies chirality rapidly from -0.947 to +0.958 backward and forward via the chirality continuum. Our demonstrations underpin the rapid development of chiral photonics and its applications.

10.
J Ethnopharmacol ; 331: 118288, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38705426

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) Xiaoer-Feire-Qing granules (XEFRQ) has been used to treat pyretic pulmonary syndrome (PPS) in children for many years. The function of the lungs is considered to be closely related to the large intestine in TCM. PURPOSE: We aimed to investigate the effects of XEFRQ on PPS and the underlying mechanisms via network pharmacology and animal experiments. METHODS: The TCMSP platform was used to identify the ingredients and potential targets of XEFRQ. The GeneCards, OMIM, and TTD databases were used to predict PPS-associated targets. Cytoscape 3.9.1 was employed to construct the protein-protein interaction network, and target prediction was performed by GO and KEGG analyses. For the animal experiment, a PPS model was constructed by three cycles of nasal drip of Streptococcus pneumoniae (STP; 0.5 mL/kg). The animals were randomly divided into the following four groups according to their weight (n = 10 rats per group): the blank group, the model group, the XEFRQ-L (16.3 g/kg) group, and the XEFRQ-H (56.6 g/kg) group. Rats in the blank group and the model group were given 0.5% CMC-Na by gavage. The general conditions of the rats were observed, and their food-intake, body weight, and body temperature were recorded for 14 days. After the intervention of 14 days, serum was collected to detect inflammatory cytokines (TNF-α, IL-1ß, and PGE2) and neurotransmitters (5-HT, SP, and VIP). H&E staining was used to observe the pathological morphology of lung and colon tissue. AQP3 expression was detected by Western blot. In addition, the gut microbiota in cecal content samples were analyzed by 16S rDNA high-throughput sequencing. RESULTS: Our network analysis revealed that XEFRQ may alleviate PPS injury by affecting the levels of inflammatory cytokines and neurotransmitters and mitigating STP-induced PPS.In vivo validation experiments revealed that XEFRQ improved STP-induced PPS and reduced the expression of inflammatory cytokines and neurotransmitters. Notably, XEFRQ significantly decreased the protein expression levels of AQP3, which was associated with dry stool. Our gut microbiota analysis revealed that the relative abundance of [Eubacterium]_ruminantium_group, Colidextribacter, Romboutsia, and Oscillibacter was decreased, which means XEFRQ exerts therapeutic effects against PPS associated with these bacteria. CONCLUSION: Our results demonstrate that XEFRQ alleviates PPS by affecting the lungs and intestines, further guiding its clinical application.


Subject(s)
Drugs, Chinese Herbal , Lung , Network Pharmacology , Rats, Sprague-Dawley , Streptococcus pneumoniae , Animals , Drugs, Chinese Herbal/pharmacology , Lung/drug effects , Lung/microbiology , Lung/pathology , Lung/metabolism , Male , Streptococcus pneumoniae/drug effects , Rats , Cytokines/metabolism , Disease Models, Animal , Protein Interaction Maps , Intestines/drug effects , Intestines/microbiology , Fever/drug therapy , Gastrointestinal Microbiome/drug effects , Lung Diseases/drug therapy , Lung Diseases/microbiology
11.
Biochimie ; 225: 26-39, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38740172

ABSTRACT

Fibroblast growth factor 21 (FGF21) is pivotal in regulating energy metabolism, highlighting substantial therapeutic potential for non-alcoholic steatohepatitis (NASH). Previously, we reported a long-acting FGF21 fusion protein, PsTag-FGF21, which was prepared by genetically fusing human FGF21 with a 648-residue polypeptide (PsTag). While this fusion protein demonstrated therapeutic efficacy against NASH, our final product analysis revealed the presence of fixed impurities resistant to effective removal, indicating potential degradation of PsTag-FGF21. Here, we enriched and analyzed the impurities, confirming our hypothesis regarding the C-terminal degradation of PsTag-FGF21. We now describe a new variant developed to eliminate the C-terminal degradation. By introducing one mutation located at the C-terminal of PsTag-FGF21(V169L), we demonstrated that the new molecule, PsTag-FGF21(V169L), exhibits many improved attributes. Compared with PsTag-FGF21, PsTag-FGF21(V169L) displayed elevated bioactivity and stability, along with a twofold enhanced binding affinity to the coreceptor ß-Klotho. In vivo, the circulating half-life of PsTag-FGF21(V169L) was further enhanced compared with that of PsTag-FGF21. In NASH mice, PsTag-FGF21(V169L) demonstrated efficacy with sustained improvements in multiple metabolic parameters. Besides, PsTag-FGF21(V169L) demonstrated the ability to alleviate NASH by decreasing hepatocyte apoptosis. The superior biophysical, pharmacokinetic, and pharmacodynamic properties, along with the positive metabolic effects, imply that further clinical development of PsTag-FGF21(V169L) as a metabolic therapy for NASH patients may be warranted.

12.
Int J Biol Macromol ; : 132291, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38816296

ABSTRACT

Arabinoxylan (AX) is a potential natural food additive that can enhance the textural properties of food. However, the addition of ascorbic acid (AA) can easily lead to a decrease in the viscosity of AX, which poses a challenge in the development of AX-rich foods. Therefore, the purpose of this study is to elucidate the mechanisms behind the reduction in AX viscosity in the presence of AA. The results indicated that AA could reduce the apparent viscosity and molecular weight of AX without significantly affecting the monosaccharide composition, suggesting a potential mechanism related to the cleavage of AX glycosidic bonds. Interestingly, free radicals were present in the reaction system, and the generation of free radicals under different conditions was consistent with the reduction in apparent viscosity of AX. Furthermore, the reduction in AX apparent viscosity by AA was influenced by various factors including AA concentration, reaction time, temperature, pH, and metal ions. These findings suggested that the mechanism of AX degradation may be due to AA-induced free radical generation, leading to non-selective attacks on glycosidic bonds. Therefore, this study revealed that the potential mechanism behind the reduction in AX viscosity induced by AA involved the generation of ascorbic acid radicals.

13.
J Am Chem Soc ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816788

ABSTRACT

Atomically precise metal nanoclusters (NCs) have become an important class of catalysts due to their catalytic activity, high surface area, and tailored active sites. However, the design and development of bond-forming reaction catalysts based on copper NCs are still in their early stages. Herein, we report the synthesis of an atomically precise copper nanocluster with a planar core and unique shell, [Cu45(TBBT)29(TPP)4(C4H11N)2H14]2+ (Cu45) (TBBT: 4-tert-butylbenzenethiol; TPP: triphenylphosphine), in high yield via a one-pot reduction method. The resulting structurally well-defined Cu45 is a highly efficient catalyst for the hydroboration reaction of alkynes and alkenes. Mechanistic studies show that a single-electron oxidation of the in situ-formed ate complex enables the hydroboration via the formation of boryl-centered radicals under mild conditions. This work demonstrates the promise of tailored copper nanoclusters as catalysts for C-B heteroatom bond-forming reactions. The catalysts are compatible with a wide range of alkynes and alkenes and functional groups for producing hydroborated products.

14.
Food Funct ; 15(11): 5868-5881, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38727142

ABSTRACT

The aim of this study was to investigate the feasibility of soy protein isolate (SPI) gels added with Tremella polysaccharides (TPs) and psyllium husk powder (PHP) as 3D printing inks for developing dysphagia-friendly food and elucidate the potential mechanism of TPs and PHP in enhancing the printing and swallowing performance of SPI gels. The results indicated that the SPI gels with a TP : PHP ratio of 3 : 7 could be effectively used as printing inks to manufacture dysphagia-friendly food. The addition of TPs increased the free water content, resulting in a decrease in the viscosity of the SPI gels, which, in turn, reduced the line width of the 3D-printed product and structural strength of the gel system. The addition of PHP increased disulfide bond interactions and excluded volume interactions, which determined the mechanical strength of SPI gels and increased the line width of the printed product. The synergistic effects between TPs and PHP improved the printing precision and structural stability. This study presents meaningful insights for the utilization of 3D printing in the creation of dysphagia-friendly food using protein-polysaccharide complexes.


Subject(s)
Deglutition Disorders , Gels , Polysaccharides , Printing, Three-Dimensional , Psyllium , Soybean Proteins , Soybean Proteins/chemistry , Polysaccharides/chemistry , Gels/chemistry , Psyllium/chemistry , Humans , Ink , Powders/chemistry , Viscosity
15.
World J Oncol ; 15(3): 521-525, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38751705

ABSTRACT

Inflammatory myofibroblastic tumors (IMTs), which involve the proliferation of fibroblastic-myofibroblastic cells mixed with inflammatory infiltrates, are exceedingly rare in the extremities. There are no reported IMTs involving the sciatic nerve. This type of involvement may cause entrapment of the sciatic nerve, whose symptoms may mimic lumbar disc herniation (LDH), especially when it occurs in patients with lumbar degenerative disc disease. We describe the case of a 40-year-old male with lumbar degenerative disc disease accompanied by IMT involving the sciatic nerve whose symptoms mimicked LDH and posed a diagnostic challenge. We showed the course of the disease as well as the systematic imaging manifestations of IMTs involving the sciatic nerve and discussed their therapeutic management.

16.
Nat Commun ; 15(1): 4562, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38811539

ABSTRACT

Two-dimensional layered organic-inorganic halide perovskites have successfully spread to diverse optoelectronic applications. Nevertheless, there remain gaps in our understanding of the interactions between organic and inorganic sublattices that form the foundation of their remarkable properties. Here, we examine these interactions using pump-probe spectroscopy and ab initio molecular dynamics simulations. Unlike off-resonant pumping, resonant excitation of the organic sublattice alters both the electronic and lattice degrees of freedom within the inorganic sublattice, indicating the existence of electronic coupling. Theoretical simulations verify that the reduced bandgap is likely due to the enhanced distortion index of the inorganic octahedra. Further evidence of the mechanical coupling between these two sublattices is revealed through the slow heat transfer process, where the resultant lattice tensile strain launches coherent longitudinal acoustic phonons. Our findings explicate the intimate electronic and mechanical couplings between the organic and inorganic sublattices, crucial for tailoring the optoelectronic properties of two-dimensional halide perovskites.

17.
Nat Commun ; 15(1): 3058, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38594271

ABSTRACT

Versatile printing of polymers, metals, and composites always calls for simple, economic approaches. Here we present an approach to three-dimensional (3D) printing of polymeric, metallic, and composite materials at room conditions, based on the polymeric vapor-induced phase separation (VIPS) process. During VIPS 3D printing (VIPS-3DP), a dissolved polymer-based ink is deposited in an environment where nebulized non-solvent is present, inducing the low-volatility solvent to be extracted from the filament in a controllable manner due to its higher chemical affinity with the non-solvent used. The polymeric phase is hardened in situ as a result of the induced phase separation process. The low volatility of the solvent enables its reclamation after the printing process, significantly reducing its environmental footprint. We first demonstrate the use of VIPS-3DP for polymer printing, showcasing its potential in printing intricate structures. We further extend VIPS-3DP to the deposition of polymer-based metallic inks or composite powder-laden polymeric inks, which become metallic parts or composites after a thermal cycle is applied. Furthermore, spatially tunable porous structures and functionally graded parts are printed by using the printing path to set the inter-filament porosity as well as an inorganic space-holder as an intra-filament porogen.

18.
High Alt Med Biol ; 2024 Apr 21.
Article in English | MEDLINE | ID: mdl-38647652

ABSTRACT

Li, Xiaoxu, Zhijun Pu, Gang Xu, Yidong Yang, Yu Cui, Xiaoying Zhou, Chenyuan Wang, Zhifeng Zhong, Simin Zhou, Jun Yin, Fabo Shan, Chengzhong Yang, Li Jiao, Dewei Chen, and Jian Huang. Hypoxia-induced myocardial hypertrophy companies with apoptosis enhancement and p38-MAPK pathway activation. High Alt Med Biol. 00:00-00, 2024. Background: Right ventricular function and remodeling are closely associated with symptom severity and patient survival in hypoxic pulmonary hypertension. However, the detailed molecular mechanisms underlying hypoxia-induced myocardial hypertrophy remain unclear. Methods: In Sprague-Dawley rats, hemodynamics were assessed under both normoxia and hypobaric hypoxia at intervals of 7 (H7), 14 (H14), and 28 (H28) days. Morphological changes in myocardial tissue were examined using hematoxylin and eosin (HE) staining, while myocardial hypertrophy was evaluated with wheat germ agglutinin (WGA) staining. Apoptosis was determined through TUNEL assays. To further understand the mechanism of myocardial hypertrophy, RNA sequencing was conducted, with findings validated via Western blot analysis. Results: The study demonstrated increased hypoxic pulmonary hypertension and improved right ventricular diastolic and systolic function in the rat models. Significant elevations in pulmonary arterial systolic pressure (PASP), mean pulmonary arterial pressure (mPAP), right ventricular mean pressure (RVMP), and the absolute value of +dp/dtmax were observed in the H14 and H28 groups compared with controls. In addition, right ventricular systolic pressure (RVSP), -dp/dtmax, and the mean dp/dt during isovolumetric relaxation period were notably higher in the H28 group. Heart rate increased in the H14 group, whereas the time constant of right ventricular isovolumic relaxation (tau) was reduced in both H14 and H28 groups. Both the right heart hypertrophy index and the heart weight/body weight ratio (HW/BW) were elevated in the H14 and H28 groups. Myocardial cell cross-sectional area also increased, as shown by HE and WGA staining. Western blot results revealed upregulated HIF-1α levels and enhanced HIF-2α expression in the H7 group. In addition, phosphorylation of p38 and c-fos was augmented in the H28 group. The H28 group showed elevated levels of Cytochrome C (Cyto C), whereas the H14 and H28 groups exhibited increased levels of Cleaved Caspase-3 and the Bax/Bcl-2 ratio. TUNEL analysis revealed a rise in apoptosis with the extension of hypoxia duration in the right ventricle. Conclusions: The study established a link between apoptosis and p38-MAPK pathway activation in hypoxia-induced myocardial hypertrophy, suggesting their significant roles in this pathological process.

19.
J Org Chem ; 89(8): 5423-5433, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38557074

ABSTRACT

Currently, most conventional methods to achieve imidazo[1,5-a]pyridines have limitations for the synthesis of 3-acyl imidazo[1,5-a]pyridines. Herein, a novel and efficient Cu(I)-catalyzed three-component annulation method for the synthesis of valuable 3-acyl imidazo[1,5-a]pyridines by the reaction of 2-pyridinyl-substituted p-QMs, terminal alkynes, and TsN3 in the presence of O2 under mild conditions have successfully been developed. The investigation indicated that molecular oxygen (O2) and TsN3, respectively, serving as oxygen and nitrogen sources, were essential for the successful completion of the reaction system.

20.
Adv Healthc Mater ; : e2304649, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38598792

ABSTRACT

Cancer immunotherapy presents a promising approach to fight against cancer by utilizing the immune system. Recently, engineered microorganisms have emerged as a potential strategy in cancer immunotherapy. These microorganisms, including bacteria and viruses, can be designed and modified using synthetic biology and genetic engineering techniques to target cancer cells and modulate the immune system. This review delves into various microorganism-based therapies for cancer immunotherapy, encompassing strategies for enhancing efficacy while ensuring safety and ethical considerations. The development of these therapies holds immense potential in offering innovative personalized treatments for cancer.

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